The high-throughput screening core will carry out the screening of small-molecule libraries against defined targets. Resources of the core at present include more than 215,000 individual, drug-like compounds, most of molecular size 250-500 daltons, and automated instrumentation for high-throughput screening utilizing optical (fluorescence, absorbance, luminescence) or solution-phase assays. Functions of the core include compound storage and handling, assay design and validation, assay execution, and data analysis. Initial optimization of validated 'hits'(compounds with activity against target) is done by screening of commercially purchased compound analogs (typically 100-500). Further 'hit-to-lead'development will be done in individual projects in consultation with the core. The core will be utilized by seven projects for compounds screening and by the five remaining projects for provision of lead compounds for testing. This core represents a unique resource in an academic environment.